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Predictive Accuracy of the Veterans Aging Cohort Study Index for Mortality With HIV Infection: A North American Cross Cohort Analysis

Justice, Amy C. MD, PhD*; P. Modur, Sharada PhD; Tate, Janet P. ScD, MPH; Althoff, Keri N. PhD, MPH; Jacobson, Lisa P. ScD, MS; Gebo, Kelly A. MD, MPH§; Kitahata, Mari M. MD, MPH; Horberg, Michael A. MD; Brooks, John T. MD#; Buchacz, Kate PhD#; Rourke, Sean B. PhD**; Rachlis, Anita MD††; Napravnik, Sonia PhD‡‡; Eron, Joseph MD‡‡; Willig, James H. MD§§; Moore, Richard PhD‖‖; Kirk, Gregory D. MD, PhD, MPH¶¶; Bosch, Ronald PhD##; Rodriguez, Benigno MD***; Hogg, Robert S. PhD†††; Thorne, Jennifer MD, PhD‡‡‡; Goedert, James J. MD§§§; Klein, Marina MD, MSc‖‖‖; Gill, John MD¶¶¶; Deeks, Steven MD###; Sterling, Timothy R. MD****; Anastos, Kathryn MD††††; Gange, Stephen J. PhDfor the NA-ACCORD and VACS Project Teams

JAIDS Journal of Acquired Immune Deficiency Syndromes: February 1st, 2013 - Volume 62 - Issue 2 - p 149–163
doi: 10.1097/QAI.0b013e31827df36c
Clinical Science

Background: By supplementing an index composed of HIV biomarkers and age (restricted index) with measures of organ injury, the Veterans Aging Cohort Study (VACS) index more completely reflects risk of mortality. We compare the accuracy of the VACS and restricted indices (1) among subjects outside the Veterans Affairs Healthcare System, (2) more than 1–5 years of prior exposure to antiretroviral therapy (ART), and (3) within important patient subgroups.

Methods: We used data from 13 cohorts in the North American AIDS Cohort Collaboration (n = 10, 835) limiting analyses to HIV-infected subjects with at least 12 months exposure to ART. Variables included demographic, laboratory (CD4 count, HIV-1 RNA, hemoglobin, platelets, aspartate and alanine transaminase, creatinine, and hepatitis C status), and survival. We used C-statistics and net reclassification improvement (NRI) to test discrimination varying prior ART exposure from 1 to 5 years. We then combined Veterans Affairs Healthcare System (n = 5066) and North American AIDS Cohort Collaboration data, fit a parametric survival model, and compared predicted to observed mortality by cohort, gender, age, race, and HIV-1 RNA level.

Results: Mean follow-up was 3.3 years (655 deaths). Compared with the restricted index, the VACS index showed greater discrimination (C-statistics: 0.77 vs. 0.74; NRI: 12%; P < 0.0001). NRI was highest among those with HIV-1 RNA <500 copies per milliliter (25%) and age ≥50 years (20%). Predictions were similar to observed mortality among all subgroups.

Conclusions: VACS index scores discriminate risk and translate into accurate mortality estimates over 1–5 years of exposure to ART and for diverse patient subgroups from North American.

*Department of Internal Medicine, Yale University and the Veterans Affairs Healthcare System, West Haven, CT

Department of Epidemiology, Johns Hopkins University, Baltimore, MD

Department of Biostatics, Yale University and the Veterans Affairs Healthcare System, West Haven, CT

§Department of Infectious Diseases, Johns Hopkins University, Baltimore, MD

Department of Allergy and Infectious Diseases, University of Washington, Seattle, WA

Division of Research, Mid-Atlantic Permanente Research Institute, Rockville, MD

#Division of HIV AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA

Departments of **Psychiatry and

††Medicine, Ontario Treatment Network, University of Toronto, Toronto, Canada

‡‡Department of Medicine, University of North Carolina Chapel Hill, Chapel Hill, NC

§§Department of Internal Medicine, University of Alabama at Birmingham, Birmingham, AL

Departments of ‖‖Medicine and

¶¶Epidemiolody, Johns Hopkins University, Baltimore, MD

##Department of Biostatiscics, Harvard Medical School, Boston, MA

***Department of Medicine, Case Western Reserve University, Cleveland, OH

†††Department of Health Sciences, British Columbia Centre for Excellence and HIV/AIDS and Simon Fraser University, Vancouver, Canada

‡‡‡Department of Ophthalmology and Epidemiology, Johns Hopkins University, Baltimore, MD

§§§Division of Cancer Epidemiology and Genetics, National Institutes of Health, Bethesda, MD

‖‖‖Department of Medicine, McGill University, Montreal, Canada

¶¶¶Department of Medicine, University of Calgary, Calgary, Canada

###Department of Medicine, University of California—San Francisco, San Francisco, CA

****Department of Medicine, Vanderbilt University, Nashville, TN

††††Department of Medicine, Einstein Medical School, New York, NY.

Correspondence to: Amy C. Justice, MD, PhD, Veterans Affairs Connecticut Healthcare System-11ACSLG, Building 35a, Room 2-212, 950 Campbell Avenue, West Haven, CT 06516 (e-mail:

Supported financially by National Institutes of Health: NIAAA (U10-AA13566), NHLBI (R01-HL095136; R01-HL090342; RCI-HL100347), and NIA (R01-AG029154; K23 AG024896). Ms. J.P. Tate was supported by the Training Program in Environmental Epidemiology funded under grant no.T32 ES07069. This work was supported by grants from the National Institutes of Health: U01-AI069918, U01-AA013566, UO1-AI-35042, 5-MO1-RR-00052 (GCRC), UO1-AI-35043, UO1-AI-35039, UO1-AI-35040, UO1-AI-35041, U01-AI38855: ALLRT; U01-AI38858; U01-AI68634; U01-AI68636; AI-69432; AI-69434, UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590, UO1-HD-32632, UL1-RR024131, P30-AI27757; K23-AI-61-0320, P30-AI27767, P30-AI50410; RR025747, P30-AI54999, R01-DA04334; R01-DA12568, R01-MH54907, R24-AI067039, N02-CP55504; Z01-CP010176, AHQ290-01-0012, K01-AI071754, K24-00432; R01-DA11602, K01-AI071725, R01 AG026250 to K.A. Gebo. This work was also supported by the Centers for Disease Control (CDC200-2006–18797), the Canadian Institutes for Health Research (CIHR: TGF-96118; HCP-97105; CBR-86906; CBR-94036; KRS-86251; 169621), and the Canadian Trials Network (project number 242).

The authors have no conflicts of interest to disclose.

The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention or those of the Veterans Affairs.

Received June 26, 2012

Accepted November 13, 2012

© 2013 Lippincott Williams & Wilkins, Inc.